Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia.

Asymmetric small interfering RNAs (asiRNAs) that mediate RNA interference have been investigated for therapeutic use in various tissues, including skin tissue. Androgenetic alopecia (AGA) is caused by a combination of genetic factors, resulting in sensitivity to dihydrotestosterone (DHT), which binds to the androgen receptor (AR) to mediate a series of biomolecular changes leading to hair loss. This study aimed to evaluate the therapeutic potential of a cell-penetrating, AR-targeting asiRNA (cp-asiAR) for AGA treatment, which was designed to silence the AR gene. AGA mouse models were developed by stimulation with DHT, and ex vivo human scalp tissues were also used for analysis. Cp-asiAR-mediated changes in mRNA expression and protein levels of AR were assessed along with the examination of phenotypic improvements in mouse model of AGA. We also assessed downstream signaling associated with AR in primary human dermal papilla (DP) cells. Several cp-asiARs were screened for selecting the optimal sequence of AR using cell lines in vitro. A cholesterol-conjugated, chemically modified cp-asiAR candidate was optimized under passive uptake conditions in vitro. Intradermal cp-asiAR injection efficiently reduced mRNA and protein levels corresponding to AR in mouse models. Moreover, cp-asiAR injection promoted hair growth in mouse models with DHT-induced AGA. In ex vivo human hair follicle culture, the proportion of telogen hair decreased, and the mean hair bulb diameter increased in the cp-asiAR-treated group. In isolated primary human DP cells, AR expression was effectively downregulated by cp-asiAR. Furthermore, cp-asiAR attenuated DHT-mediated increases in interleukin-6, transforming growth factor-ß1, and dickkopf-1 levels. No significant toxicity was observed in DP cells after cp-asiAR treatment. Cp-asiAR treatment showed effective downregulation of AR expression and prevention of DHT-mediated alterations in the hair cycle and hair diameter, indicating its potential as a novel therapeutic option for AGA.

Psychometric properties of the end-of-life care decision inventory (EOL-CDI): a mixed-methods study.

BACKGROUND: End-of-life care decision-making has become important to support dignity and quality of life for patients who are facing death in Korea, along with the enactment of the Life-Sustaining Treatment Act in 2018. However, it seems that the concepts and policies related to the law are not yet familiar to health care providers or the general public. This unfamiliarity can hinder efficient end-of-life care discussions. Therefore, the purpose of this study was to propose a valid and reliable tool to explore the level of understanding of concepts and attributes related to end-of-life care decisions. METHODS: This is a mixed-methods study design. A relevant law and literature analysis, expert consultation, cognitive interviews of 10 adults, and cross-sectional survey for psychometric tests using data from 238 clinical nurses were performed to update a tool developed before the life-sustaining treatment Act was enacted in Korea. RESULTS: 29 items of the draft version were polished in terms of literacy, total length, and scoring method via cognitive interviews and finalized into 21 items through psychometric tests and expert consultations. The 21 items conformed to the Rasch unidimensional paramenters. CONCLUSION: A tool to identify the level of understanding of concepts related to end-of-life care decisions was proposed through a rather rigorous process to ensure feasibility and validity/reliability. We recommend the proposed tool to apply to the adult population and nurses for evaluation and educational purposes.

Reliability and validity of the Self-Efficacy in Palliative Care Scale among nurses.

OBJECTIVES: To provide appropriate palliative care, nurses should have appropriate level of self-efficacy in palliative care, but the levels among nurses were low. To improve the levels effectively, self-efficacy in palliative care should be assessed using reliable and valid instruments. The purpose of this study was to examine the reliability and validity of the Self-Efficacy in Palliative Care Scale in Korean nurses. METHODS: In this cross-sectional, observational study, 272 nurses (mean age: 30 years) were enrolled from 6 university-affiliated medical centers or community hospitals in South Korea. Data on self-efficacy and demographic characteristics were collected. Validity was assessed by exploratory and confirmatory factor analyses (SPSS and Mplus). Reliability and homogeneity were assessed by Cronbach's alpha and item analyses (SPSS), respectively. RESULTS: The exploratory and confirmatory factor analyses supported the 4-factor structure (communication, assessment and symptom management, psychosocial and spiritual management of patient and family, and multiprofessional teamworking) with factor loadings >.60 and with good model fit: root mean square error of approximation =.07, Tucker-Lewis index =.94, comparative fit index =.95, and standardized root mean square residual =.04. Cronbach's alphas for the total scale and each of the subscales ranged from .883 to .965. The corrected item-total correlation coefficients of all items ranged from .61 to .90. SIGNIFICANCE OF RESULTS: The findings of this study supported the reliability and validity of this instrument among Korean nurses. This instrument can be used to assess nurses' self-efficacy in palliative care and to test intervention effects on it.

L-Type Calcium Channel Blocker Enhances Cellular Delivery and Gene Silencing Potency of Cell-Penetrating Asymmetric siRNAs.

The efficient delivery of small interfering RNAs (siRNAs) to the target cells is critical for the pharmaceutical success of RNA interference (RNAi) drugs. One of the possible strategies to improve siRNA delivery is to identify auxiliary molecules that augment their cellular uptake. Herein, we performed a chemical library screening in an effort to discover small molecules that enhance the potency of cholesterol-conjugated, cell-penetrating asymmetric siRNAs (cp-asiRNAs). Interestingly, three compounds identified from the screen share a common dihydropyridine (DHP) core and function as L-type calcium channel blockers (CCBs). Using confocal microscopy and quantitative analysis of small RNAs, we demonstrated that the L-type CCBs increased the endocytic cellular uptake of cp-asiRNAs. Furthermore, these small molecules substantially improved the potency of cp-asiRNAs, not only in vitro but also in vivo on rat skin. Collectively, our study provides an alternative pharmacological approach for the identification of small molecules that potentiate the effects of therapeutic siRNAs.

Feasibility of the Korean-Advance Directives Among Community-Dwelling Elderly Persons.

A newly developed Korean-Advance Directive (K-AD) consists of a value statement, treatment directives, and proxy appointment. It remains undetermined whether K-AD is applicable to community-dwelling persons (≥ aged 60 years). Using a descriptive study design, 275 elderly persons completed the K-AD (mean age = 77.28 ± 8.24 years). The most frequent value at the end of life was comfort dying, followed by no burden to family (23.6%). Among 4 K-AD treatment options, more than half had a preference for hospice care and had reluctance with aggressive treatment choices of cardiopulmonary resuscitation (76.4%), artificial ventilation (75.6%), and tube feeding (76.4%), with one-fifth having a desire for such options. All persons provided proxies, who were predominantly descendants (77.1%), followed by spouses (17.5%). For treatment preferences, men and those with no religion were more likely to receive life-sustaining treatments. These data support the K-AD as being applicable and acceptable among community-dwelling elderly persons; awareness of the K-AD in the community setting may facilitate future application when the need occurs.

Understanding the molecular aspects of oriental obesity pattern differentiation using DNA microarray.

BACKGROUND: Human constitution, the fundamental basis of oriental medicine, is categorized into different patterns for a particular disease according to the physical, physiological, and clinical characteristics of the individuals. Obesity, a condition of metabolic disorder, is classified according to six patterns in oriental medicine, as follows: spleen deficiency syndrome, phlegm fluid syndrome, yang deficiency syndrome (YDS), food accumulation syndrome (FAS), liver depression syndrome (LDS), and blood stasis syndrome. In oriental medicine, identification of the disease pattern for individual obese patients is performed on the basis of differentiation in obesity syndrome index and, accordingly, personalized treatment is provided to the patients. The aim of the current study was to understand the obesity patterns in oriental medicine from the genomic point of view via determining the gene expression signature of obese patients using peripheral blood mononuclear cells as the samples. METHODS: The study was conducted in 23 South Korean obese subjects (19 female and four male) with BMI ≥25 kg/m(2). Identification of oriental obesity pattern was based on the software-guided evaluation of the responses of the subjects to a questionnaire developed by the Korean Institute of Oriental Medicine. The expression profiles of genes were determined using DNA microarray and the level of transcription of genes of interest was further evaluated using quantitative real-time PCR (qRT-PCR). RESULTS AND CONCLUSION: Gene clustering analysis of the microarray data from the FAS, LDS, and YDS subjects exhibited disease pattern-specific upregulation of expression of several genes in a particular cluster. Further analysis of transcription of selected genes using qRT-PCR led to identification of specific genes, including prostaglandin endoperoxide synthase 2, G0/G1 switch 2, carcinoembryonic antigen-related cell adhesion molecule 3, cystein-serine-rich nuclear protein 1, and interleukin 8 receptor, alpha which were highly expressed in LDS obesity constitution. Our current study can be considered as a valuable contribution to the understanding of possible explanation for obesity pattern differentiation in oriental medicine. Further studies can address a novel possibility that the genomic and oriental empirical approaches can be combined and implemented in systematic and synergistic development of personalized medicine. This clinical trial was registered in Clinical Research Information Service of Korea National Institute of Health ( https://cris.nih.go.kr/cris/index.jsp ). REGISTRATION NUMBER: KCT0000387.

Effect of the guide strand 3'-end structure on the gene-silencing potency of asymmetric siRNA.

siRNAs are short dsRNAs that mediate efficient target gene silencing in a sequence-specific manner. We previously developed a novel siRNA structure, called asiRNA (asymmetric siRNA), which alleviates the off-target effects associated with conventional siRNA structures without decreasing target gene silencing potency. In the present study, we explored the effect of the guide strand 3'-end structure on the gene silencing potency of asiRNA. Interestingly, asiRNAs with a 21 nt guide strand solely composed of RNA resulted in gene silencing that was more than 6-fold more efficient compared with the corresponding asiRNA guide strand harbouring a dTdT (deoxythymidine dinucleotide) at its 3'-end. We demonstrated that the molecular basis of potency of the asiRNA with a 21 nt guide strand composed solely of RNA was due to the enhanced formation of the RISC (RNA-induced silencing complex) and increased affinity towards hAgo2 (human Argonaute2). Our observations may assist researchers in designing new asiRNAs with high on-target silencing efficiency with low off-target effects, which is critical for applications in both basic research and therapeutic development.

Long dsRNA-mediated RNA interference and immunostimulation: a targeted delivery approach using polyethyleneimine based nano-carriers.

RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via an RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as liRNA, capable of executing RNAi mediated specific target gene silencing. In this study, we developed a highly effective liRNA based targeted delivery system to apply in the treatment of glioblastoma multiforme. A stable nanocomplex was fabricated by complexing multimerized liRNA structures with cross-linked branched poly(ethylene imine) (bPEI) via electrostatic interactions. We show clear evidence that the cross-linked bPEI was quite effective in enhancing the cellular uptake of liRNA on U87MG cells. Moreover, the liRNA-PEI nanocomplex provided strong RNAi mediated target gene silencing compared to that of the conventional siRNA-PEI complex. Further, the bPEI modification strategy with specific ligand attachment assisted the uptake of the liRNA-PEI complex on the mouse brain endothelial cell line (b.End3). Such delivery systems combining the beneficial elements of targeted delivery, controlled immunostimulation, and RNAi mediated target silencing have immense potential in anticancer therapy.

Enhanced intracellular delivery and multi-target gene silencing triggered by tripodal RNA structures.

BACKGROUND: The development of gene interfering RNA (iRNA) molecules such as small interfering RNAs (siRNAs) and antagomirs provides promising therapeutic modalities for targeting specific mRNAs and microRNAs (miRNAs) involved in disease mechanisms. Therapeutic iRNA strategy against cancer or hypermutable viruses prefers targeting multiple genes simultaneously to achieve synergistic inhibition and to prevent resistance. METHODS: In the present study, we report chemically synthesized, multi-target gene interfering RNA structures based upon branched, tripodal interfering RNAs (termed T-tiRNAs). RESULTS: The T-tiRNAs could simultaneously inhibit up to three different mRNAs or miRNAs by harboring three siRNA or antagomir units. Moreover, when complexed with cationic delivery vehicles, T-tiRNAs showed enhanced gene interfering activity over conventional siRNAs or antagomirs as a result of increased intracellular delivery. CONCLUSIONS: The data obtained in the present study provide an example of synthetic multi-functional RNA structures that enable multiple gene interference in mammalian cells, which could become powerful tools for an efficient combinatorial iRNA strategy.

Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome.

Ser-5 phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by TFIIH kinase has been implicated in critical steps in mRNA synthesis, such as Pol II promoter escape and mRNA 5'-capping. However, the general requirement and precise role of TFIIH kinase in Pol II transcription still remain elusive. Here we use a chemical genetics approach to show that, for a majority of budding-yeast genes, specific inhibition of the yeast TFIIH kinase results in a dramatic reduction in both mRNA level and Ser-5 C-terminal domain phosphorylation. Surprisingly, inhibition of TFIIH kinase activity only partially affected both Pol II density and Ser-2 phosphorylation level. The discrepancy between mRNA level and Pol II density is attributed to the defective 5'-capping, which results in the destabilization of mRNAs. Therefore, contrary to the current belief, our study points strongly toward a minor role of TFIIH kinase in Pol II transcription, and a more significant role in mRNA capping in budding yeast.

Emergency Healthcare Providers' Knowledge about and Attitudes toward Advance Directives: A Cross-Sectional Study between Nurses and Emergency Medical Technicians at an Emergency Department.

This study aimed to explore and compare knowledge levels about advance directives (ADs) and life-sustaining treatment (LST) plans in end-of-life patients between emergency nurses and emergency medical technicians (EMTs). Using a cross-sectional study design and convenience sampling, 96 nurses and 68 EMTs were recruited from 12 emergency medical centers. A survey on knowledge about and attitudes toward ADs was performed using both online and offline methods between November and December 2019. Emergency healthcare providers were conceptually knowledgeable regarding ADs and LST, although approximately half or fewer had knowledge about ADs (such as the legal process for preparation, family or healthcare providers' role, and the healthcare proxy). The knowledge levels of nurses and EMTs were moderate. Nurses had significantly greater knowledge relative to EMTs about ADs and LST. Positive attitudes of emergency healthcare providers were also moderately low, with nurses having less positive views than EMTs. Significant differences regarding ADs were found, with younger emergency healthcare providers having fewer career years, no personal end-of-life experiences, and less need for ADs having less knowledge. Emergency healthcare providers' knowledge about and attitudes toward ADs were moderately low, with EMTs demonstrating a greater knowledge deficit and nurses exhibiting lower positive attitudes. Younger and novice providers had lower knowledge, but younger providers had more positive attitudes, implying that professional education and training should begin early in their careers to enhance their confidence for emergency delivery of advanced care planning.

Asymmetric shorter-duplex siRNA structures trigger efficient gene silencing with reduced nonspecific effects.

Small interfering RNAs (siRNAs) are short, double-stranded RNAs that mediate efficient gene silencing in a sequence-specific manner by utilizing the endogenous RNA interference (RNAi) pathway. The current standard synthetic siRNA structure harbors a 19-base-pair duplex region with 3' overhangs of 2 nucleotides (the so-called 19+2 form). However, the synthetic 19+2 siRNA structure exhibits several sequence-independent, nonspecific effects, which has posed challenges to the development of RNAi therapeutics and specific silencing of genes in research. In this study, we report on the identification of truncated siRNA backbone structures with duplex regions shorter than 19 bp (referred to as asymmetric shorter-duplex siRNAs or asiRNAs) that can efficiently trigger gene silencing in human cell lines. Importantly, this asiRNA structure significantly reduces nonspecific effects triggered by conventional 19+2 siRNA scaffold, such as sense-strand-mediated off-target gene silencing and saturation of the cellular RNAi machinery. Our results suggest that this asiRNA structure is an important alternative to conventional siRNAs for both functional genomics studies and therapeutic applications.

Validity and Reliability of the Life Transition Scale in Parents of Disabled Children Across the Life Transition Process.

PURPOSE: The Life Transition Scale (LTS) consists of 24 items that assess the life transition process of parents of autistic children. This study aimed to examine the validity and reliability of the LTS in parents of children with a wide spectrum of disabilities. METHODS: Data were collected from 260 parents of children with disabilities through self-report questionnaires. Validity was examined using exploratory and confirmative factor analysis to determine the factor structures of the LTS; socio-demographic differences in LTS scores were examined using the t-test or ANOVA. Reliability was examined using Cronbach's ⍺ coefficient. RESULTS: A four-factor structure was validated (x 2=640.0, p<.001, GFI=.81, RMSEA=.07, NNFI=.89, CFI=.89, PNFI=.74, Q [x 2/df]=2.60). The validity of the LTS was verified by exploratory factor analysis, with factor loading ranging from .30 to .80. There were significant differences in the accepting phase according to children's and parents' age and the type of disability, and in the wandering phase according to parental gender, educational level, job, and socioeconomic status. The Cronbach's ⍺s for the reliability of each of the four structures were acceptable, within a range of .80~.90. CONCLUSION: The LTS is a valid and reliable measurement to assess the life transition process of parents with disabled children.

Psychometric Testing of the Korean Version of the Attitudes toward the Advance Directives in Low-Income Chronically Ill Older Adults.

The purpose of this study was to examine the psychometric properties of the Advance Directive Attitude Survey in Korean (K-ADAS), a measure of attitudes toward advance directives (ADs). A total of 118 low-income, community-dwelling older adults (mean age, 75.09 years) participated. An exploratory factor analysis (EFA) was conducted to determine the factor structure of the K-ADAS. Validity was further assessed by known associations of the K-ADAS with perceived susceptibility and severity using part of the Advance Care Planning surveys. Its reliability was examined by calculating alpha coefficients. EFA determined a three-factor structure model with good model fit. Validity was further supported with significant correlations between the K-ADAS and susceptibility and severity. Reliability was supported by adequate level of Cronbach's alpha. The K-ADAS was a valid and reliable measure for assessment of AD attitudes with a sound model fit. Thus, the K-ADAS can be used to assess AD attitudes among community-dwelling elders.

HIF-1alpha-dependent gene expression program during the nucleic acid-triggered antiviral innate immune responses.

Recent studies suggest a novel role of HIF-1alpha under non-hypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers HIF-1alpha activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of HIF-1alpha protein level as well as the increase in HIF-1alpha target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated HIF-1alpha knock-down. Interestingly, HIF-1alpha knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that HIF-1alpha activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.

Correlates of advance directive treatment preferences among community-dwelling older people with chronic diseases.

BACKGROUND: Concerns over the creation of advance directives (ADs) and the factors associated with treatment directive decisions among Korean community-dwelling older people with chronic diseases have rarely been addressed. OBJECTIVES: This study aimed to examine knowledge, attitudes and barriers/benefits regarding ADs and their associations with AD treatment preferences among chronically ill, low-income, community-dwelling older people. METHODS: Using a descriptive, correlational design, older people who were recipients of home visiting service for chronic disease management participated in this study. Home visiting nurses collected data on knowledge, attitudes and perceived barriers/benefits and treatment directives using questionnaires during home visits. RESULTS: Older people (N = 112, mean age = 74.9 years, women = 83.9%) who had chronic diseases such as hypertension (56.3%), diabetes mellitus (40.2%) and cardiovascular disease/stroke (22.3%) participated. Approximately half of the participants preferred hospice care (54.5%), while a few of them preferred aggressive treatments: cardiopulmonary resuscitation (CPR) (14.3%), ventilation support (9.8%) and haemodialysis (8.9%). Being married was associated with the likelihood of preferring CPR (odds ratio [OR] = 11.79) and ventilation support (OR = 9.99), higher education with CPR (OR = 1.23) and haemodialysis (OR = 1.16), and having a cardiovascular disease (CVD)/stroke with CPR (OR = 6.46) and hospice care (OR = 3.06). Among the modifiable factors, greater perceived barriers increased the likelihood of CPR preference (OR = 1.12) but decreased the likelihood of hospice care preference (OR = 0.96). Greater perceived benefits decreased the likelihood of CPR preference (OR = 0.81) and ventilation support (OR = 0.89), and AD knowledge decreased the likelihood of haemodialysis preference (OR = 0.23). CONCLUSION: The multidimensional factors were differently associated with each of the AD treatment preferences. Modifiable factors, including perceived barriers and benefits and knowledge, should be improved to help low-income, community-dwelling older people select adequate AD treatment preferences. IMPLICATIONS FOR PRACTICE: Additional information regarding AD treatments and some modifiable and non-modifiable correlates can be integrated into primary and palliative/supportive care in public health. The current home visitation service may also benefit from incorporating AD discussions while extending the service to embrace AD issues in addition to disease management.

The role of Bach2 in nucleic acid-triggered antiviral innate immune responses.

Bach2, a bZIP transcription factor originally identified as interacting with the small Maf family of bZIP proteins, has been shown to play important roles in oxidative stress-mediated cell death. Here, we examine the role of Bach2 in cell death during double-stranded (ds)RNA- and dsDNA-triggered antiviral innate immune responses. Bach2 expression was induced in HeLa cells upon dsRNA/dsDNA treatment and the suppression of Bach2 expression by siRNA treatment alleviated cell death triggered by dsRNA and dsDNA. Unexpectedly, DNA microarray analysis revealed that siRNA-mediated suppression of Bach2 resulted in the attenuated activation of genes involved in the antiviral innate immune response after dsRNA treatment. Our study thus demonstrates a novel role for Bach2 as a key regulator of nucleic acid-triggered antiviral responses in human cells.

RNA Interference-Mediated Gene Silencing by Branched Tripodal RNAs Does Not Require Dicer Processing.

Specific gene silencing through RNA interference (RNAi) holds great promise as the next-generation therapeutic development platform. Previously, we have shown that branched, tripodal interfering RNA (tiRNA) structures could simultaneously trigger RNAi-mediated gene silencing of three target genes with 38 nt-long guide strands associated with Argonaute 2. Herein, we show that the branched RNA structure can trigger effective gene silencing in Dicer knockout cell line, demonstrating that the Dicer-mediated processing is not required for tiRNA activity. The finding of this study confirms the flexibility of the structure of RNAi triggers as well as the length of the guide strand in RNAi-mediated gene silencing.

bZIPDB: a database of regulatory information for human bZIP transcription factors.

BACKGROUND: Basic region-leucine zipper (bZIP) proteins are a class of transcription factors (TFs) that play diverse roles in eukaryotes. Malfunctions in these proteins lead to cancer and various other diseases. For detailed characterization of these TFs, further public resources are required. DESCRIPTION: We constructed a database, designated bZIPDB, containing information on 49 human bZIP TFs, by means of automated literature collection and manual curation. bZIPDB aims to provide public data required for deciphering the gene regulatory network of the human bZIP family, e.g., evaluation or reference information for the identification of regulatory modules. The resources provided by bZIPDB include (1) protein interaction data including direct binding, phosphorylation and functional associations between bZIP TFs and other cellular proteins, along with other types of interactions, (2) bZIP TF-target gene relationships, (3) the cellular network of bZIP TFs in particular cell lines, and (4) gene information and ontology. In the current version of the database, 721 protein interactions and 560 TF-target gene relationships are recorded. bZIPDB is annually updated for the newly discovered information. CONCLUSION: bZIPDB is a repository of detailed regulatory information for human bZIP TFs that is collected and processed from the literature, designed to facilitate analysis of this protein family. bZIPDB is available for public use at http://biosoft.kaist.ac.kr/bzipdb.

[Family caregivers' experiences utilizing a nursing home for their elderly family members].

PURPOSE: The purpose of this study was to explore and describe the experiences of the family caregivers using a nursing home for their elderly family members. METHOD: Participants for this study were 1 man and 9 women caregivers. Data was collected through in-depth interviews from October, 2005 to April, 2006 and analyzed using Strauss and Corbin's grounded theory methodology. RESULTS: "Finding a way to live together" emerged as a core category and it reflected expanding consciousness allowing them to see each other in a more positive view. The basic social process of "finding a way to live together" includes 3 phases: 1) recognizing the problems, 2) finding solutions to the problems, and 3) accepting the changes in their surrounding. Lack of privacy, family troubles, extreme distress, and unavailable caregivers are reflected in the process of recognizing the problems. The process of finding solutions was making a decision, obtaining family agreement, choosing the best nursing home, and enduring the financial burden. Possible outcomes of the last phase include recovering peace of mind and continuing conflict. CONCLUSION: Findings from this study offer suggestions for developing a strategy to help not only the elderly but also the family caregivers.